The overall goal of this proposal is to transition our existing Phase II COBRE research program and core facilities into a nationally recognized research center that can compete for COBRE-independent NIH center grants. During COBRE Phase I, we succeeded in developing an integrated program in CNS pathophysiology research, and built a 11,000 ft2 dedicated comprehensive neuroimaging facility called Biomedical Research and Integrative Neuroimaging (BRaIN Imaging) Center with a C06 grant from the NCRR. During Phase II, we have upgraded our state-of-the-art multimodal neuroimaging core facilities and used the facilities as the infrastructure for successfully mentoring our junior PIs. During Phase I and II, 6 out of 9 junior PIs in the COBRE successfully obtained a total of 9 new NIH R01 grants. Our peer-reviewed publications and number of grants also increased significantly. In support of this application we have obtained institutional support of ~$500,000 to upgrade our MR scanner into a phase array system and additional ~$400,000 to support the administration of the Phase III program. The funds requested in this application will be used support the Core facilities (personnel and operating costs of three cores - Magnetic Resonance Imaging (MRI), Electron Paramagnetic Resonance Imaging (EPRI) and Optical / Electrophysiology core that has a 2-photon laser scanning microscope) and a Pilot Project Program (PPP). The support of the core facilities and PPP is crucial for bringing our research program to a level competitive at the national level. During the last 8 years, our research program has evolved into four distinct topics: i) Molecular mechanism of BBB disruption;ii) Cerebral oxygenation and its potential as a viable clinical therapy;iii) Stem cells and neuroregeneration;and iv) Molecular mechanisms of neuronal injury. Our research strategy is to build a coherent, synergistic research program under the umbrella of CNS pathophysiology led by the PI of this application who will work with the group leaders of these four topics. The specific aims of the proposed Phase III COBRE are to: (1) maintain and expand the comprehensive neuroimaging core facilities that will support the conduct of basic and translational research in the area of CNS pathophysiology at UNM;and (2) sustain and expand a collaborative and multidisciplinary research environment by enhancing the focus on neuroimaging research and increasing the number of NIH-funded investigators through the proposed overall strategic planning and PPP.